Variant chr2-96861056-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000305476.10(SEMA4C):c.2072G>A(p.Arg691Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,460,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SEMA4C
ENST00000305476.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

Variant links:

Genes affected

SEMA4C (HGNC:10731): (semaphorin 4C) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SEMA4C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17106494).

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4C	NM_017789.5 linkuse as main transcript	c.2072G>A	p.Arg691Gln	missense_variant	15/15	ENST00000305476.10	NP_060259.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SEMA4C	ENST00000305476.10 linkuse as main transcript	c.2072G>A	p.Arg691Gln	missense_variant	15/15	1	NM_017789.5	ENSP00000306844	P1
SEMA4C	ENST00000467747.1 linkuse as main transcript	n.2063G>A		non_coding_transcript_exon_variant	3/3	2
SEMA4C	ENST00000474420.1 linkuse as main transcript	n.1305G>A		non_coding_transcript_exon_variant	2/2	2
SEMA4C	ENST00000482925.5 linkuse as main transcript	n.2462G>A		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

247892

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460518

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726534

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.2072G>A (p.R691Q) alteration is located in exon 15 (coding exon 14) of the SEMA4C gene. This alteration results from a G to A substitution at nucleotide position 2072, causing the arginine (R) at amino acid position 691 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.043

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.31

REVEL

Benign

0.27

Sift

Uncertain

0.010

Sift4G

Benign

0.40

Polyphen

0.82

Vest4

0.28

MVP

0.52

MPC

0.72

ClinPred

0.38

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.088

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over